P715: MULTICENTER OBSERVATIONAL STUDY OF PONATINIB IN CML PATIENTS IN ARGENTINA. REAL-WORLD EXPERIENCE.
Authors: M. J. Mela Osorio, M. V. Osycka, B. Moiraghi, M. A. Pavlovsky, A. I. Varela, I. Fernandez, F. Sackmann Massa, L. Ferrari, I. Giere, C. Sighel, M. Riddick, C. Pavlovsky
Journal: HemaSphere (2022)

Background: Ponatinib is a 3rd generation tyrosine kinase inhibitor (TKI) indicated for adults with resistant or intolerant chronic phase (CP), accelerated phase (AP) or blast phase (BP) chronic myeloid leukemia (CML) as well as in patients carrying the T315I mutation. There is a lack of data on its use in the real-world setting. Aims: We aimed to evaluate treatment patterns, outcomes and cardiovascular toxicity in CML patients treated with ponatinib in Argentina. Methods: This retrospective study included all patients aged ≥ 18 years with CP, AP and BP CML who initiated ponatinib in routine clinical practice across 2 medical centers in Argentina from 2013 to 2021. Demographic, efficacy and safety data were collected from patient medical charts. Continuous variables were dichotomized. Association was evaluated through Fisher exact test. Results: A total of 56 patients were analyzed, 53 in CP, 2 in AP and 1 in BP. One patient (1.8%) received ponatinib in first-line, 19 (34%) in second-line (2L), 35 (62.4%) in 3L, and 1 (1.8%) in ≥4L. Prior cardiovascular (CV) risk factors were recorded: hypertension 8/56 14%, body mass index ≥25kg/m2 32/56 57%, hyperlipidemia (>220mg/dl) 13/56 23.2%, smokers 10/56 18% and diabetes mellitus 4/56 7%. Median age at ponatinib start was 43.5 years (range, 18–73). Of 38 evaluated patients, 23 (60.5%) had a confirmed ABL1 mutation, including 19 (50%) with the T315I mutation. Starting doses of ponatinib were 45 mg (34%), 30 mg (53.5%), or 15 mg (12.5%). The median follow-up was 130 months (range, 13-324) and median treatment duration was 38 months (range, 1–105). At baseline, 51 patients (91%) with CP CML had less than CCyR and 2 (3.5%) were in CCyR. For 3 patients (5.3%), assessment was not available. At 3 months, 15/51 (29%) evaluable patients with CP CML were in CCyR; at 6 months, 17/44 (38.6%) evaluable patients with CP CML were in CCyR and at 12 months, 19/34 (56%) evaluable patients with CP CML were in CCyR. Additionally, 21 (37.5%) and 9 (16%) patients with CP CML achieved a major molecular response (MMR) or a deep molecular response (MR4.0–MR5.0) at least once during follow-up, respectively. Progression-free survival rates estimated for patients with CP CML at 12 and 24 months were 90.3% (95% CI, 82.6–98.8%) and 86.2% (95% CI, 77.3–96.3%), respectively. Corresponding overall survival rates were 100%, and 96.1% (95% CI, 90.9–100%). Serious arterial thrombotic adverse events (AT-AEs) occurred in 8 patients (14%), 60% of these were coronary artery disease, 30% cerebrovascular and 10% peripheral arterial disease. AT-AEs events occurred after a median time on ponatinib of 5 months (range, 2-48), the majority of the events were severe but resolved, however two were fatal. Patients who developed an AT-AE after starting ponatinib were older than 60 years (p=0.0174), and had higher cholesterol levels (p=0.03979). No associations were found regarding obesity (p=0.403), previous TKI lines (p>0.5), smoking history (p>0.5) or ponatinib starting dose ≤30mg vs >30mg (p=0.4248). Summary/Conclusion: This is the first analysis of ponatinib treated patients in real-world in Argentina and demonstrates that ponatinib has a favorable efficacy and safety profile in patients with CML treated in standard clinical practice. Cardiovascular toxicity of ponatinib in routine clinical practice is increased. Older (>60y) and dyslipemic patients were at higher-risk of occlusive events. Prompting aggressive control of CV risk factors as well as reducing doses at optimal time-points may help optimize the use of ponatinib during daily practice.